From: judgeparker23x@gmail.com   
      
   Scientific Reports   
   Article | OPEN   
      
   Different Brain Regions are Infected with Fungi in Alzheimer’s Disease   
   Diana Pisa, Ruth Alonso[…]Luis Carrasco   
   Scientific Reports 5, Article number: 15015 (2015)   
   doi:10.1038/srep15015   
   Download Citation   
   Fungal immune evasionFungi   
   Received:   
   19 May 2015   
   Accepted:   
   15 September 2015   
   Published online:   
   15 October 2015   
   Abstract   
   The possibility that Alzheimer’s disease (AD) has a microbial aetiology has   
   been proposed by several researchers. Here, we provide evidence that tissue   
   from the central nervous system (CNS) of AD patients contain fungal cells and   
   hyphae. Fungal    
   material can be detected both intra- and extracellularly using specific   
   antibodies against several fungi. Different brain regions including external   
   frontal cortex, cerebellar hemisphere, entorhinal cortex/hippocampus and   
   choroid plexus contain fungal    
   material, which is absent in brain tissue from control individuals. Analysis   
   of brain sections from ten additional AD patients reveals that all are   
   infected with fungi. Fungal infection is also observed in blood vessels, which   
   may explain the vascular    
   pathology frequently detected in AD patients. Sequencing of fungal DNA   
   extracted from frozen CNS samples identifies several fungal species.   
   Collectively, our findings provide compelling evidence for the existence of   
   fungal infection in the CNS from AD    
   patients, but not in control individuals.   
      
   Introduction   
   Neurodegenerative diseases constitute a heterogeneous group of disorders of   
   the central nervous system (CNS) that are characterised by a slow and   
   irreversible loss of neuronal functions. The aetiology of primary   
   neurodegenerative diseases, such as    
   Alzheimer’s disease (AD), multiple sclerosis (MS), Parkinson’s disease   
   (PD) and amyotrophic lateral sclerosis (ALS), remains largely unknown. A   
   common feature of many neurodegenerative diseases is the presence of   
   aggregates of misfolded proteins (   
   intracellular inclusions) in regions of the CNS that can serve as   
   neuropathological hallmarks for disease diagnosis1,2. Depending on the   
   particular disease, these insoluble fibrillar aggregates can vary in   
   distribution and composition3.    
   Histopathologically, AD is characterised by the accumulation of intracellular   
   tangles of hyperphosphorylated tau protein and extracellular deposits of   
   amyloid protein4,5. Proteolytic processing of membrane-associated amyloid   
   precursor protein (APP)    
   results in the generation of neurotoxic amyloid β (Aβ) peptide6,7, which is   
   the major component of the distinctive senile plaques in AD. The cytotoxicity   
   induced by Aβ pepetide involves disruption of calcium homeostasis, oxidative   
   stress, synaptic    
   dysfunction and neuronal loss8,9,10. The prevailing dogma to explain the   
   pathogenesis of AD is that the accumulation of amyloid deposits formed by Aβ   
   pepetide may induce intracellular tangles of tau protein that in turn leads to   
   neuronal death11.    
   However, the so-called “amyloid hypothesis” has been questioned by several   
   findings including the failure of clinical trials aimed to lower amyloid   
   deposits or tau tangles12,13,14. Moreover, many elderly people with normal   
   cognitive function have    
   substantial amyloid burden in their CNS11. At present, there is no therapy to   
   stop or reverse the symptoms of AD. Aside from cognitive decline, the vast   
   majority of AD patients present clear signs of inflammation and damage to   
   blood vessels15,16.    
   Inflammation of the CNS and immune activation play a major role in the   
   pathophysiology of AD. Indeed, a number of cytokines, such as interleukins   
   (IL-1 and IL-6), tumor necrosis factor α and interferon γ, are elevated in   
   the brain of AD patients,    
   suggesting an increased immune response17,18,19. These observations have led   
   to the speculation that AD has an autoimmune aetiology20. Many investigators   
   have also considered the idea that AD is an infectious disease, or at least   
   that infectious agents    
   constitute a risk factor for AD21,22,23. Accordingly, genetic material from   
   several viruses and bacteria have been reported in brains from AD patients. In   
   particular, herpes simplex type 1 (HSV-1) and Chlamydophila pneumoniae have   
   been suggested as    
   potential aetiological agents of AD. In addition, brain infection by several   
   pathogens may induce amyloid formation24,25,26. Furthermore, Αβ peptide   
   exhibits antimicrobial activity and shows particularly strong inhibitory   
   activity against Candida    
   albicans27.   
      
   Recently, we provided strong evidence for fungal infection in AD   
   patients28,29. Fungal DNA and proteins were found in frozen brain tissue from   
   AD patients, but not from control patient tissue. Moreover, fungal material   
   could be detected intra- and    
   extracellularly in neurons from AD patients. In the present work, we have   
   examined in detail the presence of fungal structures in different regions of   
   the brain of an AD patient by immunohistochemistry. No fungal material was   
   observed in brain tissue    
   from ten control individuals, whereas fungal infection was clearly present in   
   brains from ten additional AD patients. Moreover we were able to amplify   
   fungal DNA from frozen tissue of different AD brain regions. Collectively, our   
   findings provide    
   compelling evidence for the presence of fungal infection in brains from all AD   
   patients analysed.   
      
   Results   
   Fungal structures in AD CNS   
      
   [continued in next message]   
      
   --- SoupGate-Win32 v1.05   
    * Origin: you cannot sedate... all the things you hate (1:229/2)